Introducing Schizophrenia

1. Introducing Schizophrenia Dr Eddy Mellor

2. Historical background • First descriptions of symptoms appear in ancient Greek texts • Changing attitudes in the 18th century led to an increase interest in studying mental illness; previously there behaviour was regarded as reprehensible • The discovery of the pathology and treatment of general paresis of the insane led Emil Kraepelin to identify another unique syndrome which he named Dementia Praecox

3. “On the one hand we observe a weakening of those emotional activities which permanently form the mainsprings of volition. In connection with this , mental activity and instinct for occupation become mute. The result of this part of the process is emotional dullness, failure of mental activities, loss of mastery of volition, of endeavour and of ability for independent action. The essence of personality is thereby destroyed, the best and most precious part of being; torn from her….” • Kraepelin Dementia Praecox 1919

4. Epidemiology • Schizophrenia is a world wide public health concern being present in all countries and cultures • Interestingly its incidence is almost uniform across geographical, cultural and religious borders • Just less than 1% of people suffer from schizophrenia, if the schizophrenia spectrum disorders are included this rises to 5%

5. Almost equal sex distribution with a slight excess of male patients. • Females tend to develop the disease on average 4 years later than males • Female distribution of the disease also shows a second “spike” at menopause • Also a third spike occurs for both sexes at around 60-65 years, these patients are termed late onset schizophrenia. Many clinicians view this as a distinct clinical entity to schizophrenia.

7. Aetiology • Several models which can be grouped into…. • Biological • Social • Psychological

8. Biological theories • Again the precise aetiology remains unknown but there is good evidence to support a biological cause for Schizophrenia and several promising lines of enquiry • Many people would regard schizophrenia as a syndrome. A collection of disease entities producing similar clinical picture but with distinct aetiologies. Much like Learning disability being classified a s a single disease entity before a plethora of causes were identified

9. Genetics • Family twin and adoptive studies have shown beyond doubt that a large degree of risk of Schizophrenia is genetically determined • Risk as high as 55% for identical twins. Around 15 5 if one parent is affected rising to almost 40% if both parents affected

11. Eight linkage sites have thus far been identified on the 1st 6th 8th 10th thirteenth and 15th chromosomes. • Several specific genes have also been identified each of which confers a degree of vulnerability to the disease • Although genetic studies do support a biological causation they also demonstrate that other factors must be involved as many genetically risky individuals never develop schizophrenia.

12. Pathology contribution • Post mortem studies of schizophrenic brains first identified morphological features of the condition • Brains show enlarged lateral ventricles at PM and reduced volume of hypocampus • There brains are lighter than controls • Newer imaging techniques have shown a more rapid reduction of cortical volume during first illness episode

13. Identified risks • A number of interesting possibilities supported by studies… • An excess of birth and gestational complications leading some to postulate anoxic brain injury as a risk factor • An excess of winter births of individuals with the disease has led to speculation of a viral or post-viral autoimmune process

14. Studies of incidence rates have also shown an increased incidence of children who were in utero during influenza epidemics • The same has also been demonstrated for children born during times of famine. • Another risk factor which has shown statistical significant association is that children with rhesus incompatibility also show an increased risk

15. The Dopamine hypothesis • “normal” individuals exposed to dopamine releasing drugs such as amphetamines over a period of days will develop a psychosis clinically indistinguishable from schizophrenia which generally disappears with abstinence from the drugs • All effective antipsychotic drugs have dopamine blocking properties

16. Overactivity in dopaminergic meso-frontal and mesocortical neurones and their associated dopamine-D2 receptors has been suggested as the basis of “positive” features of schizophrenia such as acute hallucinations and delusions. • When psychotic scizophrenic patients are given amphetamine they release substantially more dopamine than healthy controls.

17. Beyond the dopamine hypothesis • The improvement in “negative” features (such as lack of volition or planning ability) achieved by the newer atypical antipsychotic drugs suggests that neuronal pathways other than just dopaminergic ones are important in some of the symptoms schizophrenia.

18. Neuro-cognitive testing • Schizophrenic patients perform worse as a group on all neuropsychological tests compared to IQ matched controls. • First degree relatives also perform worse on average than controls

19. Social • Studies have shown an excess of schizophrenic patients in lower socioeconomic groups and in urbanised areas. This used to be attributed to “social drift” • Newer studies following children from various backgrounds suggest this is not the case and living in a highly urbanised area is indeed a risk factor for schizophrenia

20. Psychosocial • abnormalities in processing sensory information, in separating “signal from background noise”, or in manipulating abstract information • Consistently demonstrate “Jump to conclusion” reasoning or JTC • Excess life traumas against controls at first presentation

21. Clinical features • The prodrome- Increasingly recognised is a prodromal state of 1-2 years duration preceding the onset of psychosis • Typical features of the prodrome are: anxiety, depression, reduced concentration, difficulty communicating ,reduced motivation and suspiciousness • Brief and transitory psychotic ideas lasting minutes or hours may also feature

22. These problems often lead to a reduced level of functioning and may lead to unemployment or below expected educational achievement • When taking a history from a patient with new onset psychosis establishing a prodromal phase raises suspicion of a diagnosis of Scizophrenia • Collateral history is often of value in screening for prodromal symptom's

23. ICD-10 criteria-1 • Based on First Rank symptoms described by Kurt Schneider, German Psychiatrist • There are two groups of symptoms: • Major: at least one of these must be present to make a diagnosis of schizophrenia • Minor: at least two of these must be present to make a diagnosis. • These symptoms must be present most of the time for at least one month

24. Schneider’s 1st Rank Symptoms • Schneider’s 1st Rank Symptoms • Auditory Hallucinations: running • commentary, discussing him among • themselves, thought echo • Thought insertion, withdrawal, broadcast • Passivity phenomena: actions, feelings • Delusional perception: a normal perception • happens, and a delusional interpretation is • attached to it.

25. Major symptoms/signs • 1-Thought echo, thought insertion, withdrawal or broadcasting • 2-Delusional perception OR delusions of control (passivity phenomena) • 3-Hallucinatory voices: Running commentary, discussing him among themselves or coming from some part of the body. • 4-Delusions that are culturally inappropriate & completely impossible, e.g.: controlling weather

26. Minor Symptoms • Persistent hallucinations in any modality, everyday for at least 1 month, when accompanied by delusions without affective content • Neologisms, incoherent/irrelevant speech • Catatonic behaviour (excitement, mutism….) • Negative symptoms (apathy, paucity of • speech, etc) which are not due to • depression or medication side effect.

27. Symptom development and Dopamine • Understanding the normal function of Dopamine in the brain is key to understanding the psychopathology of schizophrenia • Dopamine is released in the healthy subject in response to innately rewarding or adverse events. • An example would be playing a difficult level on a computer game and unexpectedly succeeding. • Another would be in response to seeing on hearing footsteps behind you in a dark alley.

28. In the schizophrenic patients brain, during a psychotic episode, dopamine can be released at any time and can lead to the individual falsely attributing significance or fear to objects, sensory information or thoughts. • They may for instance get a feeling of intense significance, such as one might get when the killer is unmasked in a murder mystery, whilst looking at a car number plate.

29. Alternatively they might get a surge of dopamine whilst concentrating on their own thoughts and interpret their thoughts as alien, (thought insertion) • They could get a surge of dopamine whilst watching television and suddenly feel they are somehow related to or responsible for the death of Michael Jackson or the Credit Crunch

30. Using this model it is easy to see how anyone could quickly build up a complex delusionary system. We all want to make sense of what is happening around us and we all trust our own senses. • Patients delusions are often built up from a single or several unusual experiences which they then try and rationalise. • If you heard voices that no one else could hear would it not be preferable to think it was a microchip implanted in your skull rather than face up to the fact you might be mentally ill?

31. Prognosis/ course • 1/3 recover; 1/3 relapse and remit; 1/3 become chronic 6-10% suicide • Increased rates violence about 5x to carers and staff, least often strangers • Similar number to suicide dies prematurely from physical illness • Increased rates dependent living, homelessness, unemployment • As become older negative symptoms increase whilst positive symptoms diminish

32. Investigation • As always in psychiatry your first objective should be to exclude an organic problem • In the case of patient presenting with symptoms suggestive of schizophrenia there are two important organic differential diagnosis • A Drug induced psychosis can closely resemble a schizophrenia presentation

33. Undiagnosed temporal lobe epilepsy can present in a similar way to an acutely psychotic patient • Always complete a urine drug screen on admission, Amphetamines can be clear from the urine in 48 hours • Patients should routinely have an ECG at first presentation • ALWAYS complete a thorough neurological exam rarely malignancy can masquerade as psychosis

34. Differential diagnosis • Acute & Transient Psychotic Disorders • Persistent Delusional Disorder • Bipolar Disorder (manic or mixed episode with • psychosis) • Severe Depressive Episode (with psychosis) • Schizo-affective Disorder • Drug Induced Psychosis • Organic Delusional Disorder: epilepsy; brain • tumours, etc • Delirium • Dementia

35. Differential Diagnosis 2 • Schizotypal Disorder • Personality Disorders • Paranoid • Schizoid • Emotionally unstable, borderline type • Dissociative Disorders • Malingering

36. Sub types • Classically divided into four sub types • Paranoid • Hebephrenic • Simple or undifferentiated • Catatonic

37. Paranoid type • Relatively stable, often persecutory delusions • Usually hallucinations, particularly of the auditory variety, and other perceptual disturbances • Affect, volition and speech disturbances, and catatonic symptoms are either absent or inconspicuous.

38. Hebephrenic Schizophrenia • Prominent affective changes • delusions and hallucinations: fleeting/rudimentary • Irresponsible and unpredictable behaviour • Mannerisms • Shallow and inappropriate mood • Disorganised thought • Incoherent speech • Social isolation • Usually poor prognosis (because of the rapid • development of "negative" symptoms, particularly • flattening of affect and loss of volition

39. Catatonic Schizophrenia Prominent psychomotor disturbances that may alternate between extremes such as violent excitement & stupor, or automatic obedience & negativism. Constrained attitudes and postures may be maintained for long periods. Uncommon in industrialised countries

40. Undifferentiated Schizophrenia • Psychotic conditions meeting the general • diagnostic criteria for schizophrenia but not • conforming to any of the other subtypes, or • exhibiting the features of more than one of • them, without a clear predominance of a • particular set of diagnostic characteristics.

41. Treatment • Treatment & Management • This should be again 3-fold: Bio-psychosocial • Medication • Risk reduction (to himself & others) • Observation • Psychology (CBT for delusions) • Occupational therapy • Family therapy • Social integration

42. Medication-1 • ►Older anti-psychotics (conventional) vs • newer anti-psychotics • ►Older ones had more side effects (Extrapyramidal • Side Effects [EPSEs]) • ►Anti-muscarinic meds are used to counter • EPSEs (eg: procyclidine, orphenadrine, etc) • ►Newer ones are much more expensive • ►Depot vs Oral

43. Clozapine • Targets Serotonin 2 receptors and D4 • receptors; the ordinary old and new • antipsychotics target D2 receptors. ►NICE advises to use Clozapine, once 2 • different anti-psychotics (of 2 different • groups) have been tried for appropriate • periods (each 6-12 weeks) and the • psychosis continues termed treatment resistant scizophrenia.

44. Medication-ECG • Possibly serious ECG abnormalities • At least once yearly ECGs requiresd • QTc prolongation: the normal range is from 370 • ms to 450 in men & 470 in women. • If pre-existing abnormalities, more prone for • Sudden Cardiac Death. • Consider referral or senior review if not sure

45. Neuroleptic Malignant syndrome • Potentially fatal complication of antipsychotic use • More common in neuroleptically naïve patients • Presents with- Severe muscle rigidity, High fever, mutism, delirium. • Caused by muscle break down leading to Rhabdomyalysis

46. Patient will often appear confused and may be agitated • The clinical picture may be mistaken for catatonia or acute psychosis • Bloods will show a marked elevation in Ck in the 1000s • It is a medical emergency and patient’s will require fluids and may need dialysis, urgent transfer to medical unit is indicated

47. Tarditive dyskinesia • Distressing condition in which involuntary movements (chewing, sucking grimacing) occur persistently • This occurs more commonly with typical antipsychotic drugs and is usually first noticed when stopping or changing medication • Believed to be caused by dopamine hypersensitisation no universally effective treatment exists.